Molecular profile of MSH6-associated colorectal carcinomas shows distinct features from other Lynch syndrome-associated colorectal carcinomas

Molecular tumour pathology - and tumour genetic

Mismatch repair deficiency and MUTYH variants in small intestine-neuroendocrine tumors

& nbsp;Small intestine-neuroendocrine tumors (SI-NETs) are one of the most common tumors of the small bowel. Despite an increasing incidence, the exact mechanisms driving underlying pathology remain to be determined. Interestingly, recent studies linked the development of (SI-)NETs to both Lynch syndrome (LS) and MUTYH variants. If confirmed, these associations would have important consequences for treatment. In this study we therefore investigated the prevalence of mismatch repair (MMR) deficiency and MUTYH variants in 64 primary resected SI-NETs. Immunohistochemistry was used to assess the expression of the MMR genes, and competitive allele-specific PCR (KASPar) targeting two hotspot MUTYH variants [p.(Tyr179Cys), p.(Gly396Asp)] was performed to determine their prevalence in SI-NETs. Strikingly, all 64 SI-NETs stained positive for MSH6 and PMS2, indicating & nbsp;MMR proficiency. In addition, no MUTYH hotspot variant was found in any of the 64 SI-NETs. As such, these results do not support an association between SI-NET development and LS or MUTYH variants. In order to gain insight into SI-NET pathogenesis and optimally manage patients, future research should therefore focus on other candidate genes. (C) 2022 Published by Elsevier IncMTG2 - Moleculaire genetica van gastrointestinale tumorenMolecular tumour pathology - and tumour genetic

Autoantibodies involved in primary and secondary adrenal insufficiency following treatment with immune checkpoint inhibitors

Primary and secondary adrenal insufficiency (AI) are commonly known immune-related adverse events following treatment with immune checkpoint inhibitors (ICIs), and are clinically relevant due to their morbidity and potential mortality. For this reason, upfront identification of patients susceptible for ICI-induced AI could be a step in improving patient’s safety. Multiple studies have focused on the identification of novel biomarkers for ICI-induced AI, including autoantibodies, which may be involved in ICI-induced AI as a result of the T-cell-mediated activation of autoreactive B cells. This review highlights the currently described autoantibodies that may be involved in either primary [e.g. anti-21-hydroxylase, anti-17α-hydroxylase, anti-P450scc, anti-aromatic L-amino acid decarboxylase (AADC), anti-interferon (IFN)α and anti-IFNΩ] or secondary AI [e.g. anti-guanine nucleotide-binding protein G(olf) subunit alpha (GNAL), anti-integral membrane protein 2B (ITM2B), anti-zinc finger CCHC-type containing 8 (ZCCHC8), anti-pro-opiomelanocortin (POMC), anti-TPIT (corticotroph-specific transcription factor), anti-pituitary-specific transcriptional factor-1 (PIT-1) and others], and discusses the current evidence concerning their role as biomarker for ICI-induced AI. Standardized autoantibody measurements in patients (to be) treated with ICIs would be a clinically accessible and patient-friendly screening method to identify the patients at risk, and could change the management of ICI-induced AI

The effect of chlorhexidine varnish on root caries: a systematic review

Item does not contain fulltextOBJECTIVE: The aim of this study was to systematically review the present literature on the effect of chlorhexidine varnish (CHX-V) on root caries. MATERIALS AND METHODS: The MEDLINE-PubMed, the Cochrane-CENTRAL and EMBASE databases were searched through December 2010 to identify any appropriate studies. Root caries incidence and root caries activity were selected as outcome variables. RESULTS: An independent screening of the unique titles and abstracts of 24 MEDLINE-PubMed, 14 Cochrane-CENTRAL and 18 EMBASE papers resulted in 6 publications that met the eligibility criteria. Data extraction provided no conclusive evidence that the application of CHX-V is effective in patients when regular professional oral prophylaxis is performed. If effective, the 40% CHX-V was found to provide a benefit over a control or fluoride varnish. CHX-V at lower concentrations (1 and 10%) may provide protection against root caries in high-risk patients (such as geriatric and xerostomia patients) in the absence of regular professional oral prophylaxis. CONCLUSION: Within the limitations of this review, it may be concluded that in the absence of regular professional tooth cleaning and oral hygiene instructions, CHX-V may provide a beneficial effect in patients in need of special care. The strength of this recommendation is graded as 'weak'